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FEBS Lett. 2000 Jul 28;478(1-2):100-4.

Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA.

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1
Institut für Biochemie, Linikum der RWTH Aachen, Pauvelsstr, 30, 52057 Aachen, Germany.

Abstract

Prior activation of mitogen-activated protein kinases by phorbol 13-myristate 12-acetate (PMA) results in an inhibition of interleukin (IL)-6-induced activation of the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway which is most likely mediated by the induction of suppressor of cytokine signaling-3 and requires the specific SHP2 binding site Y759 of the IL-6 signal transducer gp130. In this study, we demonstrate that PMA inhibits STAT activation by IL-6 and the related cytokine leukemia inhibitory factor (LIF) but not by oncostatin M (OSM). Since the LIF receptor also contains an SHP2 recruitment site whereas the OSM receptor lacks such a module, we propose that two SHP2 binding modules within a homo- or heterodimeric receptor are necessary to mediate the PMA inhibitory effect.

PMID:
10922477
[Indexed for MEDLINE]
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